Simon T. Hodgson

The protecting–directing role of the trityl group in syntheses of pyrrole derivatives: efficient preparations of 1-H-pyrrole-3-carboxylic acid and 3-acyl-, 3-amino-, and 3-bromo-1-tritylpyrroles

Trifluoroacetylation, formylation, and bromination of 1-tritylpyrrole occur regioselectively at the 3-position in high yields. Quantitative hydrolysis of the 3-trifluoroacetyl derivative and removal of the trityl group from the resulting acid with sodium in liquid ammonia furnishes a new, short, high-yielding synthesis of the simple 1-H-pyrrole-3-carboxylic acid. 1-Tritylpyrrole-3-carboxylic acid has been converted efficiently into 3-aminopyrroles via Curtius rearrangement of the derived azide: 3-amino-1-tritylpyrrole appears to exist in solution exclusively as its imino-Δ4-pyrroline tautomer. 1-H-3-t-Butyloxycarbonylaminopyrrole undergoes trifluoroacetylation regioselectively at the 2-position. Metallation of 1-tritylpyrrole with butyl-lithium in hexamethylphosphoric triamide gives rise to the unexpected products 9-phenylfluorene, 1-methoxycarbonylpyrrole and methyl triphenylmethylacetate (after work-up of the lithiointermediates with carbon dioxide and methylation of the resulting acids).The mechanism proposed for the reductive cleavage of the trityl group in 1-tritylpyrrole is supported by the results of cyclic voltammetry experiments.

π-Allyltricarbonyliron lactone complexes in synthesis: application to the synthesis of the β-lactam antibiotic (+)-thienamycin

Synthesis of an enantiomerically pure β-lactam intermediate used in the preparation of the antibiotic (+)-thienamycin is described, by suitable elaboration of a functionalised π-allyltricarbonyliron complex.

Use of π-allyltricarbonyliron lactam complexes in the preparation of nocardicin derivatives: synthesis of (−)-3-oxo-1-[(p-benzyloxyphenyl)-benzyloxycarbonylmethyl]azetidin-2-one

A short five-step synthesis, in 79% overall yield, of (–)-3-Oxo-1 -[(p-benzyloxyphenyl) benzyloxy-carbonylmethyl]azetidin-2-one (3), a precursor for nocardicin synthesis has been developed from isoprene monoepoxide. The key steps of the procedure rely on the efficient transformation of 2–4-η3-(1-formyloxy-2-methylbut-3-en-2-ylato)tricarbonyliron into the corresponding diastereoisomeric lactam complexes (6) and (7) using D-(–)-benzyl-(p-benzyloxyphenyl)glycinate (5) and ZnCl2·TMEDA (TMEDA = tetramethylethylenediamine), and their oxidation with ceric ammonium nitrate to 3-isopropenylazetidinone derivatives.

Synthesis of marine toxins. A biomimetic approach to the novel spirobenzoquinonefuran stypoldione

A synthesis of the spirobenzoquinonefuran unit, i.e.(10), present in stypoldione, a novel marine toxin found in the brown alga Stypopodium zonale which shows pronounced narcotic and hyperactive effects upon reef-dwelling fish, is described. The synthesis uses a strategy, viz(17)→(18)→(19)→(11)→(10), which has close similarities to the probable biogenesis of this portion of the natural product (scheme 1). The advanced precursors (30) and (36) for projected syntheses of deoxystypoldione (33) and stypodiol (3) respectively were also prepared, but neither substrate underwent polyene cyclization to the required pentacyclic molecules.

Synthesis of ?-lactams from ?-allyltricarbonyliron (lactone) complexes

Several π-allyltricarbonyliron (lactone) complexes have been treated with an excess of benzylamine in the presence of Lewis acids to afford the corresponding lactam complexes by an SN2′-like process. These lactam complexes were oxidised in good yield with ceric ammonium nitrate to provide a novel route to a variety of β-lactam compounds. Simple chemical transformations of the resulting β-lactams have been investigated; these include the conversion of the vinyl and isopropenyl side chains into hydroxyethyl substituents and the reductive removal of benzyl groups to afford the parent NH β-lactams.